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Collation Model for Oversize LJS 266: La generacion de Adam [manuscript].
Get PDFCollection of genealogical and chronicle material, including Biblical genealogy from Adam to Jesus and the apostles; genealogy concerning the Trojan War and the founding of Rome; the legendary history of England and France as founded by descendants of participants in the Trojan War, including the genealogy of Brut and the succeeding line of kings in England up to Coyl; the emperors of Rome; the Holy Emperors starting with Charlemagne; and the kings of France up to Charles V (crowned 1364). The introduction (f. 1r) suggests that the manuscript was meant to trace the kings of England through Richard II (1377-1399) and the popes through one named Innocent and therefore that the manuscript is incomplete.https://repository.upenn.edu/sims_models/1007/thumbnail.jp
Collation Model for Oversize Ms. Codex 1081: De consolatione philosophiae [manuscript].
Get PDFPhilosophical dialogue in five books between a narrator and Lady Philosophy which deals with ideas of fate, fortune, and the relationship between free will and divine omniscience, and which was one of the most important philosophical texts of the medieval period, includes marginal notations drawn from Nicholas Trivet; and a list of books in a personal library being taken to Salamanca (f.86v).https://repository.upenn.edu/sims_models/1016/thumbnail.jp
Essays on Banking and Credit Markets
No full textThis dissertation focuses on two themes in the field of empirical banking. First, the importance of credit relationships for corporations experiencing financial distress; second, the relevance of credit market structure for the price and non-price terms associated with the provision of credit. The first chapter investigates whether relationship lending helps firms experiencing idiosyncratic financial distress. By constructing a novel dataset on syndicated lending that tracks the availability and pricing of credit for US corporate borrowers over three decades, I conclude that relationship lending benefits borrowers in distress. Specifically, I find that relationship lenders provide a higher credit amount, charge lower interest rates, and require similar collateral and fees, relative to non-relationship lenders. Firms benefit from relationship lending irrespective of their access to outside financing options. Overall, my findings provide support to theories of implicit commitment and reputational capital in lending relationships. The second chapter focuses on the importance of bank specialization in monitoring specific projects for the design of loan contracts. Using detailed information on credit relationships in the US syndicated loan market, I first document that banks specialize in lending to specific industries. Specialization is common across industries and persistent over time. Then, I provide evidence that specialized banks provide credit with looser restrictions (covenants) and at lower cost (interest rates) when arranging loans in their sector of specialization. This is consistent with an explanation of bank specialization based on monitoring advantages. Overall, the laxer contract terms offered by specialized banks could provide an explanation for recent evidence that firms cannot easily substitute credit granted by specialized banks
Essays on the Economics of Disaster Risk
No full textThis dissertation explores disaster risk in the context of a changing climate, imperfect public policies, and frictions that limit the capitalization of current and future climate risk in housing markets. The chapters\u27 results suggest how better provision of information and policies that internalize homeowners\u27 and lenders\u27 climate exposure can ameliorate the costs of climate change in real estate markets. In my first chapter, I study the economic consequences of using better flood risk models to more accurately identify and price flood insurance for high-risk homes. I estimate my results with administrative flood insurance policy data and a novel survey measuring flood insurance demand, risk perceptions, and objective risk. To identify the effects of risk information, I use variation created by outdated elevation data and risk models that caused high-risk homes to be misclassified as low-risk. My findings show that flood risk classification provides valuable information not only for insurers, but also for homeowners. Misclassifying high-risk homes as low-risk causes owners to underestimate their current and future flood risk, invest less in risk-reducing adaptation, and buy less flood insurance despite substantially lower premiums. Embedding these estimates in a sufficient statistics model with dynamic risk and endogenous risk beliefs and adaptation, I find that identifying and pricing the estimated six million high-risk homes outside the floodplain would increase social welfare by \$138 billion. In the second chapter, co-authored with Professor Benjamin Keys, we explore dynamic changes in the capitalization of sea level rise (SLR) risk in housing and mortgage markets. Our results suggest a disconnect in coastal Florida real estate: From 2013-2016, home sales volumes in the most-SLR-exposed communities declined 20\% relative to less-SLR-exposed areas, even as their sale prices grew in lockstep. By 2019, however, relative prices in these at-risk markets finally declined 5\% from their peak. Over this period, home sellers accumulated an excess inventory of unsold properties as they maintained high list prices and transaction volumes declined. Lender behavior cannot reconcile these patterns, as both all-cash and mortgage-financed purchases similarly contracted, with little increase in loan denials or securitization. We propose a demand-side explanation for our findings where SLR risk has become more salient in the home price expectations of prospective buyers than sellers. The lead-lag relationship between transaction volumes and prices in SLR-exposed markets is consistent with dynamics at the peak of prior real estate bubbles. In the third chapter, co-authored with Dr. Yanjun Liao, we study how home equity influences homeowners\u27 decisions to insure flood risk. We show that low home equity is an important driver of low flood insurance take-up. To isolate the causal effect of home equity on flood insurance demand, we exploit price changes over the housing boom and bust. Insurance take-up follows house price dynamics closely, with a home price elasticity around 0.3. Multiple mechanism tests show evidence consistent with a debt overhang channel, whereby uninsured households with low equity rely on mortgage default to manage their flood risk. As a result, households do not fully internalize their disaster risk
Understanding the Role of Nuclear Acetyl-CoA Synthetase 2 in Maintaining Histone Acetylation
No full textHistone acetylation is governed by nuclear acetyl-CoA pools generated in part from local acetate by metabolic enzyme acetyl-CoA synthetase 2 (ACSS2). We hypothesize that during gene activation, a local transfer of intact acetate occurs via sequential action of epigenetic and metabolic enzymes. Using stable isotope labeling, we detect transfer between histone acetylation sites both in vitro using purified mammalian enzymes and in vivo using quiescence exit in Saccharomyces cerevisiae as a change-of-state model. We show that Acs2, the yeast orthologue of ACSS2, is recruited to chromatin during quiescence exit, and observe dynamic histone acetylation changes proximal to Acs2 peaks. We find that Acs2 is preferentially associated with the most upregulated genes, suggesting that acetyl-group transfer plays an important role in gene activation. Overall, our data reveal direct transfer of acetate between histone lysine residues to facilitate rapid transcriptional induction, an exchange that may be critical during changes in nutrient availability.Since ACSS2 does not have known DNA- or histone-binding domains, we hypothesize that it associates with chromatin indirectly through other transcription factors or chromatin modifying enzymes. We performed immunoprecipitation experiments coupled to mass spectrometry in neuronal cell lines and mouse models and identified nuclear accumbens associated 1 (NACC1) as a novel interactor. We determined nuclear localization of both ACSS2 and NACC1 in differentiated cells through proteomics experiments. Moreover, we have found ACSS2 and NACC1 chromatin-bound during differentiation and enriched near genes of cell-cell adherens, cytoplasmic, and membrane, which are important in differentiation and formation of neuronal processes. Our findings highlight a potential mechanism for ACSS2 recruitment to during critical metabolic changes such as neuronal differentiation
Understanding the Relationship between Clot Contraction and Platelet Biology under Hemodynamic Conditions
No full textAs thrombosis proceeds, platelets in a clot can expose phosphatidylserine (PS), providing a negatively charged surface for thrombin generation. These PS+ platelets have been shown to sort to the perimeter of platelet masses via platelet contraction. However, it remains unclear how thrombin and fibrin affect PS+ platelet sorting within a clot. We used an 8-channel microfluidic device to perfuse blood over collagen/TF to evaluate temporal and spatial PS+ platelet sorting. We found that thrombin inhibition, fibrin polymerization inhibition, or fibrinolysis each increased clot contraction and PS sorting. Fibrin attenuated clot contraction and PS sorting. Clots without fibrin had a 3.6-times greater contraction than clots with fibrin. Based on these results, we wanted to study contraction further. We tested the effect of inhibitors of ADP and/or thromboxane A2 (TXA2) signaling on clot contraction. We developed two automated imaging methods to score fluorescent platelet percent contraction: (1) “global” measurement of clot length, and (2) “local” changes in surface area coverage of platelet aggregates within the clot. Total platelet fluorescence and global aggregate contraction were highly correlated (R2 = 0.87). Local aggregate contraction was more pronounced than global aggregate contraction across all inhibition conditions. Conditions with TXA2 inhibition were shown to significantly reduce local aggregate contraction relative to conditions without TXA2, unlike conditions with ADP inhibition. Lastly, we recently obtained a glycoprotein VI (GPVI) inhibitor. GPVI is a collagen receptor on platelets that drives platelet activation; however, its role at later stages in clotting remains unclear. We tested the effect of anti-GPVI Fab on PS exposure, which occurs at later stages of platelet activation. On collagen/TF, Fab present at t = 0s reduced PS exposure, but had no effect when added 30 or 90 seconds later. Thrombin generated via PS exposure had an important role in driving platelet deposition when Fab was present, since inhibition of PS via annexin V binding in the presence of Fab significantly inhibited platelet deposition. Our results from these studies help elucidate the relationship between platelet activation, PS exposure, fibrin, and clot contraction
Unlocking New Odd-Electron Pathways via Photoactive Catalysis
No full textIn the past decade, renewed interest in odd-electron pathways has reaffirmed organic chemistry’s indispensable role in the synthesis of complex molecules and in drug-discovery efforts. Odd-electron intermediates unlock reactivity patterns that are not observed in two-electron processes and offer complementary chemoselectivity. Importantly, these processes are often “blind” to the source of radical and can thus be adapted toward a diverse array of chemical feedstocks. Photoredox catalysis harnesses radicals in a controlled, predicable manner and can be used to orchestrate elaborate radical and polar bond-forming processes, which allowed the development of the radical-polar crossover annulation reaction (RPAR) paradigm. Furthermore, these catalysts, in conjunction with transition metal complexes, enable multiple C-C bond-forming events in so-called dicarbofunctionalization (DCF) reactions, and can even be used to functionalize commodity materials via photochemical C-H abstraction. Visible light can also be used to excite electron donor-acceptor complexes in the absence of a photocatalyst to permit radical generation. This mode of reactivity has provided an avenue to new bioisosteric space via the late-stage introduction of bicyclo[1.1.1]pentyl (BCP) motifs. Finally, photochemically-initiated hydrogen-atom transfer (HAT) catalysis can be harnessed to access strong single-electron reductants that permit the single C-F bond activation of trifluoroacetates and -acetamides. This has allowed facile access to gem-difluoromethylene containing compounds that are challenging to prepare by state-of-the-art methods. Discoveries in each of these arenas will be discussed
Extracting Generalizable Hierarchical Patterns of Functional Connectivity in the Brain
No full textThe study of the functional organization of the human brain using resting-state functional MRI (rsfMRI) has been of significant interest in cognitive neuroscience for over two decades. The functional organization is characterized by patterns that are believed to be hierarchical in nature. From a clinical context, studying these patterns has become important for understanding various disorders such as Major Depressive Disorder, Autism, Schizophrenia, etc. However, extraction of these interpretable patterns might face challenges in multi-site rsfMRI studies due to variability introduced due to confounding variability introduced by different sites and scanners. This can reduce the predictive power and reproducibility of the patterns, affecting the confidence in using these patterns as biomarkers for assessing and predicting disease. In this thesis, we focus on the problem of robustly extracting hierarchical patterns that can be used as biomarkers for diseases. We propose a matrix factorization based method to extract interpretable hierarchical decomposition of the rsfRMI data. We couple the method with adversarial learning to improve inter-site robustness in multi-site studies, removing non-biological variability that can result in less interpretable and discriminative biomarkers. Finally, a generative-discriminative model is built on top of the proposed framework to extract robust patterns/biomarkers characterizing Major Depressive Disorder. Results on large multi-site rsfMRI studies show the effectiveness of our method in uncovering reproducible connectivity patterns across individuals with high predictive power while maintaining clinical interpretability. Our framework robustly identifies brain patterns characterizing MDD and provides an understanding of the manifestation of the disorder from a functional networks perspective which can be crucial for effective diagnosis, treatment and prevention. The results demonstrate the method\u27s utility and facilitate a broader understanding of the human brain from a functional perspective
Collation Model for Oversize Ms. Codex 1122: Topica ... [etc.] [manuscript].
Get PDFA treatise on rhetorical theory written for C. Trebatius Testa in 44 B.C. Cicero\u27s work is based on the work of the same name by Aristotle. Several pages (f. 3r-5v) of annotations have been added, which come from Boethius\u27s In Ciceronis topica. The treatise is prefaced in this codex by a letter to Trebatius (which can be found in the collection of Cicero\u27s letters as Ad familiares 7.19) explaining Cicero\u27s reasons for writing and instructions for reading.https://repository.upenn.edu/sims_models/1034/thumbnail.jp
Penn Library\u27s Ms. Codex 1668 - Cabale misterieuse des 150 pseaumes du Roy David (Video Orientation)
No full texthttps://repository.upenn.edu/sims_video/1146/thumbnail.jp